Capsules for pharmaceutical preparations and neutraceutical preparations are generally prepared using gelatin and hydroxypropyl methylcellulose (HPMC) as base materials.
Gelatin capsules have high industrial productivity and high price competitiveness. However, if gelatin capsules contain 10 wt % moisture or less, they may lose plasticity and may show serious deterioration in impact resistance. Concern on mad cow diseases has limited the use of gelatin capsules. For these reasons, plant-based HPMC capsules prepared without gelatin have drawn attention.
According to gelation properties, hard capsule preparation methods may be roughly classified into two methods: cold gelation and thermal gelation.
First, cold gelation involves: heating a solution including a gelatin that may gelate at room temperature, or an HPMC solution containing carrageenan, agar, sodium alginate, gellan gum, and/or pectin that may gelate at room temperature; maintaining the solution at a high temperature to age it; immersing a cold mold pin in the solution so that the mold pin is coated with a predetermined amount of the solution; and removing the mold pin from the solution, immediately applying cold air at a temperature of about 20° C. to the solution on the mold pin to gelate the gelatin or HPMC of the solution, and drying the gel. Gelating agents such as carrageenan, sodium alginate, gellan gum, pectin, or the like are widely used in cold gelation to form capsules because they have increased gelation capability due to bonding to metal ions, such as potassium, calcium, and sodium. However, when a capsule including foreign substances, such as carrageenan, is orally administered, the foreign substances may react with metal salts in gastric juice or intestinal juice, so that a binding force among components of the capsule may be increased, thereby inhibiting the capsule from disintegrating.
Next, thermal gelation is based on the gellation characteristics of HPMC in a solution when heated at high temperatures. A high-temperature mold pin is immersed in an HPMC solution maintained at a temperature higher than or equal to room temperature so as to be coated with the HPMC solution, and HPMC of the HPMC solution coated on the mold pin is gelated by the heat of the mold pin, thereby preparing hard capsules.
However, if the capsules are disintegrated by gastric juice, they may not be used as capsules for pharmaceutical or neutraceutical preparations when the main ingredients and excipients of the preparations filled in the capsule are unstable to acid, or may cause stomach irritation or an odor generated therefrom to regurgitate. To solve the above problems, the surfaces of the capsules containing ingredients may be coated with an enteric base material to give enteric properties.
However, the method of coating capsules with an enteric base material may require an additional coating process and increase production costs. Furthermore, an organic solvent in a coating solution is highly likely to remain on the capsule surface after the coating, capsule identification codes on the surfaces may not be visible due to the coating, or the capsules may have poor appearance, as compared to before the coating.
To address these drawbacks, many researchers have been tried to develop various kinds of enteric capsules. However, enteric hard capsules with high quality and high industrial productivity have not yet been commercialized.